Nizatidine is the generic name given to the compound N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl -2-nitro-1,1-ethenediamine, an anti-ulcer compound taught by Pioch in U.S. Pat. No. 4,375,547. The patent discloses the synthesis of nizatidine by the reaction of 4-[[(2-aminoethyl)thio]-methyl]-N,N-dimethyl-2-thiazolemethanamine with 1,1-dimethylthio-2-nitroethene to provide the corresponding 2-nitro-1-methylthio-1-etheneamine derivative, which is subsequently converted to nizatidine upon reaction with monomethylamine. The process disclosed in the patent produces methanethiol gas as a by-product, which is known to produce an unpleasant odor that requires the use of extra purification equipment to eliminate.
The present invention relates to a process for preparing N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-2-nitro-1 -phenoxy-1-etheneamine comprising reacting 4-[[(2-aminoethyl)thio]methyl]-N,N-dimethyl-2-thiazolemethanamine with 1,1-diphenoxy-2-nitroethene in an aprotic solvent. The present invention also provides the product of the present process as an additional embodiment. The present process does not produce methanethiol gas, and is therefore an especially valuable process for preparing nizatidine on a large scale wherein cost is an important consideration.